In the canine cell line MDCK, endogenous CBLL1 (Hakai), a...

In the canine cell line MDCK, endogenous CBLL1 (Hakai), an E3 ubiquitin ligase, interacts with endogenous CDH1 (E-cadherin) at the plasma membrane (Fujita et al. 2002). The interaction between endogenous canine CBLL1 and CDH1 in MDCK cells is stimulated by hepatocyte growth factor, a ligand for MET and EGFR receptor tyrosine kinases, suggesting that the interaction is dependent on tyrosine phosphorylation (Fujita et al. 2002). Two tyrosine residues in the juxtamembrane domain of a recombinant mouse CDH1 (Y755 and Y756), which are subject to phosphorylation by a recombinant avian SRC, are needed for binding of the endogenous recombinant mouse CBLL1 when all three proteins are expressed in human HEK293 cell line (Fujita et al. 2002). In human breast cancer cell line MCF7, binding of CBLL1 to CDH1 is stimulated by calcium depletion-mediated activation of CDC42 RHO GTPase and the consequent SRC activation (Shen et al. 2008). In human hepatocellular carcinoma cell line HepG2, activation of SRC and FYN kinases, which can be triggered by the integrin-interacting protein BSG (also known as Basigin or CD147) (Lu et al. 2018) stimulates binding of the endogenous CBLL1 and CDH1 (Chen et al. 2009; Lu et al. 2018). In the human colon carcinoma cell line T84, IFNG (inteferfon-gamma)-stimulates binding of CBLL1 to CDH1, which is dependent on the tyrosine phosphorylation of CDH1 by FYN kinase (Smyth et al. 2012). Overexpression of a recombinant mouse CBLL1 in MDCK cells reduces the interaction between endogenous canine CTNND1 and CDH1, suggesting that binding of CBLL1 and CTNND1 to CDH1 are mutually exclusive (Fujita et al. 2002). Based on the crystal structure of a recombinant mouse CBLL1, CBLL1 functions as a Zn2+-coordinated homodimer (Mukherjee et al. 2012). Using a recombinant mouse CBLL1 and a recombinant human CDH1, it was reported that the minimum CDH1 phosphotyrosine-binding sequence in CBLL1 is within amino acid residues 148-206, while CDH1 phosphorylated tyrosine residue Y754 is essential for CBLL1 binding (Mukherjee et al. 2012: recombinant avian SRC was used for CDH1 phosphorylation).